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Modulation of gut microbiota contributes to effects of intensive insulin therapy on intestinal morphological alteration in high-fat-diet-treated mice

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Abstract

Aims

Disturbance of intestinal homeostasis promotes the development of type 2 diabetes. Although intensive insulin therapy has been shown to promote extended glycemic remission in newly diagnosed type 2 diabetic patients through multiple mechanisms, its effect on intestinal homeostasis remains unknown.

Methods

This study evaluated the effects of intensive insulin therapy on intestinal morphometric parameters in a hyperglycemic mice model induced by high-fat diet (HFD). 16S rRNA V4 region sequencing and multivariate analysis were utilized to evaluate the structural changes of gut microbiota.

Results

HFD-induced increases in the lengths of villus, microvillus and crypt depth were significantly reversed after intensive insulin therapy. Moreover, intestinal proliferation was notably decreased after intensive insulin therapy, whereas intestinal apoptosis was further increased. Importantly, intensive insulin therapy significantly shifted the overall structure of the HFD-disrupted gut microbiota toward that of mice fed a normal diet and changed the gut microbial composition. The abundances of 54 operational taxonomic units (OTUs) were changed by intensive insulin therapy. Thirty altered OTUs correlated with two or more intestinal morphometric parameters and were designated ‘functionally relevant phylotypes.’

Conclusions

For the first time, our data indicate that intensive insulin therapy recovers diabetes-associated gut structural abnormalities and restores the microbiome landscape. Moreover, specific altered ‘functionally relevant phylotypes’ correlates with improvement in diabetes-associated gut structural alterations.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China Grant Awards (81770819, 81570737, 81370947, 81570736, 81500612, 81400832, 81600637, 81600632 and 81703294), the National Key Research and Development Program of China (2016YFC1304804 and 2017YFC1309605), the Jiangsu Provincial Key Medical Discipline (ZDXKB2016012), the Key Project of Nanjing Clinical Medical Science, Jiangsu Province Key Research and Development Program (BE2016606), the Jiangsu Provincial Medical Talent (ZDRCA2016062), the Natural Science Foundation of Jiangsu Province of China (BK20170125), the Jiangsu Provincial Medical Youth Talent (QNRC2016020, QNRC2016019 and QNRC2016018), the Medical Scientific Research Foundation of Jiangsu Province of China (Z201610 and Q2017006), the Science and Technology Project of Administration of Traditional Chinese Medicine of Jiangsu Province of China (YB2015072), the Six Talent Peaks Project of Jiangsu Province of China (WSN-165 and SWYY-091), the Fundamental Research Funds for the Central Universities (021414380444, 021414380092, 021414380208, 021414380160, 021414380142, 021414380279, 021414380296 and 021414380317), the Nanjing Science and Technology Development Project (ZKX16036, YKK16105 and 201605019) and the Nanjing Health Youth Talent (QRX17123).

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Authors and Affiliations

  1. Department of Endocrinology, Drum Tower Hospital Affiliated to Nanjing University Medical School, 321 Zhongshan Road, Nanjing, 210008, China

    Hongdong Wang, Wenjuan Tang, Pengzi Zhang, Zhou Zhang, Jielei He, Dalong Zhu & Yan Bi

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  1. Hongdong Wang
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  2. Wenjuan Tang
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  3. Pengzi Zhang
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  4. Zhou Zhang
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Correspondence to Yan Bi.

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All animal studies were conducted according to guidelines established by the Research Animal Care Committee of Drum Tower Hospital Affiliated to Nanjing University Medical School.

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This article belongs to the topical collection "Gut Microbiome and Metabolic Disorders" managed by Massimo Federici

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Wang, H., Tang, W., Zhang, P. et al. Modulation of gut microbiota contributes to effects of intensive insulin therapy on intestinal morphological alteration in high-fat-diet-treated mice. Acta Diabetol 57, 455–467 (2020). https://doi.org/10.1007/s00592-019-01436-0

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